BACKGROUND:Cellular senescence,which triggers the aging process of physiological decline in the body,is closely related to osteoporosis.With the development of aging research,significant progress has been made in the study of targeted clearance of senescent cells.Accordingly,senolytic cell therapy for osteoporosis based on this has attracted increasing attention.Current research on the association between aging and osteoporosis shows the characteristic of multidisciplinary intersection.However,existing reviews are mostly based on a single database(such as PubMed)and lack a systematic comparative analysis of Chinese and English literature.Therefore,it is of great academic value to integrate resources from multiple databases and systematically reveal the research status and hot trends of aging in the field of osteoporosis research.OBJECTIVE:To summarize the development,current status,hotspots,and future trends of research on aging in the field of osteoporosis over the past 20 years,so as to provide references for future related research.METHODS:We searched for research literature on the correlation between aging and osteoporosis in CNKI,WanFang,VIP and Web of Science Core Database.The search time span was from August 1,2004 to September 24,2024.Then,we used NoteExpress 4.0 for data cleaning and CiteSpace 6.3R1(Advanced)and Excel(2024)for literature analysis.RESULTS AND CONCLUSION:Since 2004,research on the correlation between aging and osteoporosis has shown a significant growth trend.Bibliometric analysis shows that(as of September 2024),and 1 275 English documents and 151 Chinese documents have been published,with the highest number of publications in China and the United States.In terms of publishing institutions,the Mayo Clinic ranked first,followed by Shanghai Jiao Tong University and the University of California system.As for core authors,Sundeep Khosla and Joshua Nicholas Farr were the authors with the most publications and citations,while Pei Lingpeng and Hui Bodi were the most worthy of attention in Chinese literature.After the keywords"aging"and"osteoporosis"and their synonyms were excluded,it was found that cellular senescence,senescence-associated secretory phenotype,signaling pathways,and targeted senolytic cell clearance therapy haven been the current research hotspots and theoretical frontiers.

BACKGROUND:Cellular senescence,which triggers the aging process of physiological decline in the body,is closely related to osteoporosis.With the development of aging research,significant progress has been made in the study of targeted clearance of senescent cells.Accordingly,senolytic cell therapy for osteoporosis based on this has attracted increasing attention.Current research on the association between aging and osteoporosis shows the characteristic of multidisciplinary intersection.However,existing reviews are mostly based on a single database(such as PubMed)and lack a systematic comparative analysis of Chinese and English literature.Therefore,it is of great academic value to integrate resources from multiple databases and systematically reveal the research status and hot trends of aging in the field of osteoporosis research.OBJECTIVE:To summarize the development,current status,hotspots,and future trends of research on aging in the field of osteoporosis over the past 20 years,so as to provide references for future related research.METHODS:We searched for research literature on the correlation between aging and osteoporosis in CNKI,WanFang,VIP and Web of Science Core Database.The search time span was from August 1,2004 to September 24,2024.Then,we used NoteExpress 4.0 for data cleaning and CiteSpace 6.3R1(Advanced)and Excel(2024)for literature analysis.RESULTS AND CONCLUSION:Since 2004,research on the correlation between aging and osteoporosis has shown a significant growth trend.Bibliometric analysis shows that(as of September 2024),and 1 275 English documents and 151 Chinese documents have been published,with the highest number of publications in China and the United States.In terms of publishing institutions,the Mayo Clinic ranked first,followed by Shanghai Jiao Tong University and the University of California system.As for core authors,Sundeep Khosla and Joshua Nicholas Farr were the authors with the most publications and citations,while Pei Lingpeng and Hui Bodi were the most worthy of attention in Chinese literature.After the keywords"aging"and"osteoporosis"and their synonyms were excluded,it was found that cellular senescence,senescence-associated secretory phenotype,signaling pathways,and targeted senolytic cell clearance therapy haven been the current research hotspots and theoretical frontiers.

ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated liver cirrhosis， as well as the impact of recompensation on the prognosis of such patients， and to provide a basis for early identification of high-risk patients in clinical practice. MethodsA retrospective analysis was performed for the clinical data of patients who attended The Third People’s Hospital of Kunming from January 2016 to December 2022 and were diagnosed with decompensated liver cirrhosis due to hepatitis B， hepatitis C， alcoholic hepatitis， and autoimmune hepatitis， and they were divided into recompensation group and persistent decompensation group. To control for confounding factors， whether recompensation occurred was used as the rouping variable，and BMI， alcohol consumption history， HIV infection history， TG， CHOL， LDL， and HDL were used as covariates. The propensity score was calculated， and 1：1 nearest neighbor matching was performed with a caliper value of 0.1. After propensity score matching， the recompensation group and the persistent decompensation group with relatively balanced covariates were obtained. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the influencing factors for recompensation； the “rms” package was used to establish a nomogram； the receiver operating characteristic （ROC） curve was plotted to calculate the area under the ROC curve （AUC）； the Hosmer-Lemeshow test was used to assess the goodness of fit of the model； the “Calibration Curves” package was used to plot calibration curves for model assessment. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of survival curves. ResultsAmong the 863 patients with decompensated liver cirrhosis， 305 experienced recompensation， resulting in an incidence rate of 35.3%. After PSM， 610 cases were successfully matched， with 305 cases in each group. The univariate and multivariate Cox regression analyses showed that etiology （hepatitis C： hazard ratio［HR］=0.288， P=0.002）； male（HR=0.701， P=0.016）， age（HR=0.988， P=0.047）， hemoglobin （HGB）（HR=1.006， P=0.017）， and CD4 T cell（HR=1.001，P=0.047）， TIPS procedure （HR=1.808，P=0.042） were independent influencing factors for recompensation in patients with decompensated liver cirrhosis. During follow-up， 116 patients died of liver disease-related causes， with 27 patients （8.85%） in the recompensation group and 89 （15.95%） in the persistent decompensation group； 109 patients developed HCC， with 23 patients （7.54%） in the recompensation group and 86 （15.41%） in the persistent decompensation group. The Kaplan-Meier survival curves showed significant separation between the patients with different states of compensation in terms of liver disease-related mortality rate and the incidence rate of HCC， and the Log-rank test showed that there were significant differences between the two groups in liver disease-related mortality rate （χ²=9.023， P=0.003） and the incidence rate of HCC （χ²=10.526， P=0.001）. ConclusionEtiology，sex，age，TIPS，HGB，and CD4 T cell are independent influencing factors for recompensation in patients with decompensated liver cirrhosis. There is a significant difference in the incidence rate of recompensation between decompensated liver cirrhosis patients with different etiologies， and female patients and patients with a younger age，a history of TIPS， a higher HGB level， and a higher CD4 lymphocyte count are more likely to experience recompensation. Recompensation is the key to improving the long-term prognosis of patients and can significantly reduce long-term liver disease-related mortality rate and the incidence rate of HCC.

Objective To explore the changes in intrarenal pelvic pressure and intrarenal temperature during F6.3 disposable electronic ureteroscopic lithotripsy through in vitro experiments. Methods Microchannels were established in the upper, middle, and lower calyces of ex vivo porcine kidneys. Spherical calcium oxalate stones(size:0.5 cm×0.5 cm×0.5 cm, 1-2 per target calyx)were placed via the microchannels. Temperature and pressure sensors were connected through sheaths and placed in each calyx. F6.3 disposable electronic ureteroscope combined with super-pulsed thulium fiber laser(pulse energy:0.1 J, frequency:300 Hz, power:30 W)was used for laser lithotripsy. During the procedure, normal saline(25±1)℃ was used for irrigation at a gradient of 10-150 mL/min(increasing by 10 mL/min). The temperature and pressure in the upper, middle, and lower calyces were observed and recorded at different irrigation flow rates, with each experiment repeated five times, and the average value was calculated. The intrarenal temperature and pressure changes within and between the three groups were compared. Results In the ex vivo porcine kidney model, intrarenal pelvic pressure increased linearly with the increase in irrigation flow rate. When the flow rate reached 90 mL/min, the average intrarenal pelvic pressure was(28.8±1.16)mmHg. When the flow rate was increased to 100 mL/min, the pressure exceeded the safety threshold, reaching(31.23±1.12)mmHg. With the increase in irrigation flow rate, intrarenal temperature gradually decreased. When the flow rate reached 20 mL/min, the maximum intrarenal temperature was 45.1 ℃. When the flow rate was increased to 30 mL/min, the maximum intrarenal temperature was 40.9 ℃, which did not exceed the safety threshold(43 ℃). Conclusion The in vitro experiments demonstrated that during F6.3 disposable electronic ureteroscopic lithotripsy, maintaining an irrigation flow rate of 30-90 mL/min kept the intrarenal pelvic pressure and intrarenal temperature within the safety thresholds, indicating that the procedure is safe and reliable.

IL-32 is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory properties.It has been proved that expression of IL-32 increases with progression of gastric mucosal diseases and severity of gastric cancer(GC),thus participating in process of gastric"inflammation-cancer"transformation.However,how IL-32 affects malignant transformation of gastric"inflamma-tion-cancer"and finally leads to adverse outcome of GC invasion and migration is still controversial.In order to better clarify regulatory effect and possible mechanism of abnormal expression of IL-32 on different histopathological stages of gastric"inflammation-cancer"transformation,and to explore new directions and breakthroughs in molecular mechanism of early truncation and treatment of gastric precancerous lesion(GPL),we searched literatures related to IL-32 in six authoritative databases at home and abroad,such as Pubmed,Web of Science and CNKI,in past 30 years.It was found that pathogenicity or protective function of IL-32 in different histo-pathological stages of gastric"inflammation-cancer"transformation depended on its different subtypes,secretory forms,surrounding cytokine environment,disease status and genetic factors.IL-32 may regulate polarization of macrophages through NF-κB,MAPK,COX2,PR3,IDO,NOD,PKCδ,FAK and STAT3,amplify or inhibit chronic inflammatory stimulation of gastric mucosa,and thus participate in process of gastric"inflammation-cancer"transformation.Our new understanding of role of IL-32 in different stages of Cor-rea cascade may contribute to development of cytokine-directed therapy,and therapy aimed at regulating different alternative splicing subtypes of IL-32 and targeting IL-32 signals can be used as a new strategy for medical treatment of GPL and GC in future.

IL-32 is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory properties.It has been proved that expression of IL-32 increases with progression of gastric mucosal diseases and severity of gastric cancer(GC),thus participating in process of gastric"inflammation-cancer"transformation.However,how IL-32 affects malignant transformation of gastric"inflamma-tion-cancer"and finally leads to adverse outcome of GC invasion and migration is still controversial.In order to better clarify regulatory effect and possible mechanism of abnormal expression of IL-32 on different histopathological stages of gastric"inflammation-cancer"transformation,and to explore new directions and breakthroughs in molecular mechanism of early truncation and treatment of gastric precancerous lesion(GPL),we searched literatures related to IL-32 in six authoritative databases at home and abroad,such as Pubmed,Web of Science and CNKI,in past 30 years.It was found that pathogenicity or protective function of IL-32 in different histo-pathological stages of gastric"inflammation-cancer"transformation depended on its different subtypes,secretory forms,surrounding cytokine environment,disease status and genetic factors.IL-32 may regulate polarization of macrophages through NF-κB,MAPK,COX2,PR3,IDO,NOD,PKCδ,FAK and STAT3,amplify or inhibit chronic inflammatory stimulation of gastric mucosa,and thus participate in process of gastric"inflammation-cancer"transformation.Our new understanding of role of IL-32 in different stages of Cor-rea cascade may contribute to development of cytokine-directed therapy,and therapy aimed at regulating different alternative splicing subtypes of IL-32 and targeting IL-32 signals can be used as a new strategy for medical treatment of GPL and GC in future.

Objective To assess stromal fibrosis in epidermal growth factor receptor(EGFR)mutant lung adenocarcinoma and its association with resistance to targeted therapy and patient prognosis.Methods Medical records of 207 patients diagnosed with EGFR-mutant advanced lung adenocarcinoma who received treatment at a hospital between January 2021 and December 2022 were reviewed.A total of 86 patients were ultimately included based on their prognosis and survival duration.These patients were categorized into a resistance group(32 cases)and a non-resistance group(54 cases),depending on whether they developed resistance to targeted therapy within one year.Additionally,patients were classified into mild,moderate,and severe fibrosis groups according to the extent of fibrosis observed.Clinical and pathological characteristics,as well as fibrosis levels,were compared between the two groups.Factors influencing the development of resistance to targeted therapy in patients with EGFR-mutant lung adenocarcinoma were analyzed,and the survival outcomes of patients with varying degrees of fibrosis were evaluated during follow-up.Results In the resistance group,the prevalence of EGFR exon 20 insertion mutations,elevated CA125 levels,and the presence of moderate-to-severe fibrosis were significantly higher compared to the non-resistance group(P<0.05).Multivariate logistic regression analysis revealed that EGFR exon 20 inser-tion mutation(OR=3.691,95%CI:1.043～13.057),elevated CA125 levels(OR=4.104,95%CI:1.160～14.517),and moderate-to-severe fibrosis(OR=3.959,95%CI:1.410～11.115)were independent risk factors associated with resistance to targeted therapy among patients with EGFR-mutant lung adenocarcinoma(P<0.05).The Cox proportional hazards model demonstrated a C-index of 0.72(95%CI:0.65～0.79),with area under the curve(AUC)values for 1-year and 2-year survival predictions of 0.781 and 0.734,respectively.EGFR exon 20 insertion mutation(HR=3.691),moderate-to-severe fibrosis(HR=3.959),and elevated CA125 levels(HR=4.104)were identified as independent prognostic factors for overall survival in these patients following targeted therapy.The median progression-free survival(PFS)for patients with mild,moderate,and severe fibrosis was 10.5 months,7.2 months,and 3.9 months,respectively,while the median overall survival(OS)was 21.4 months,16.1 months,and 11.5 months,respectively.Statistically significant differences in both PFS and OS were observed across the three fibrosis severity groups.(P<0.05).Conclusion The extent of stromal fibrosis in EGFR-mutant lung adenocarcinoma influences resistance to targeted therapy,and the progression of fibrosis is correlated with an unfavorable prognosis.

Objective To investigate the causal relationship between obstructive sleep apnea(OSA)and common types of dementia by using Mendelian randomization(MR)analysis methods.Methods Based on summary data from large-scale genome-wide association studies(GWAS),single nucleotide polymorphisms(SNP)highly associated with OSA,Alzheimer's disease(AD),vascular dementia(VaD),dementia with Lewy bodies(DLB),and frontotemporal dementia(FTD)were selected as instrumental variables.The inverse variance weighted method(IVW)was employed as the primary analytical method,and stability tests were conducted by using the simple median method,weighted median method(WME),MR-Egger regression meth-od,simple mode(SM)and weighted mode(WM).Additionally,F-statistics,Cochran'Q test,MR-Egger re-gression intercept test,and leave-one-out method were used for weak instrument variables bias testing,hetero-geneity testing,pleiotropy analysis,and sensitivity analysis,respectively.Causal associations were evaluated by using odds ratios(OR)and 95%CI.Results MR analysis showed that OSA was associated with an increased risk of VaD(OR=1.829,95%CI:1.024-3.266,P<0.05).All F-statistics were>10,indicating no weak in-strumental variables.Cochran'Q test and MR-Egger regression intercept test revealed no heterogeneity and horizontal pleiotropy(P>0.05).Conclusion Genetic-level prediction suggests that OSA is associated with an increased risk of VaD.Early prevention and treatment of OSA may help improve patients'quality of life.

Objective: To investigate the predictive value of EZH2 expression for malignant transformation in oral leukoplakia (OLK) and to provide a reference for clinical practice. Methods: This study was approved by the institutional ethics committee, and informed consent was obtained from all participants. A total of 114 patients diagnosed with OLK by pathological examination and treated at our hospital between November 2020 and July 2022 were initially enrolled. After excluding those with incomplete data or follow-up, 105 participants were included in the final analysis, comprising 14 in the high EZH2 expression group and 91 in the low EZH2 expression group. Histopathological examination of oral mucosa and immunohistochemical detection of EZH2 protein expression were performed. The follow-up period was 30 months; participants were followed until malignant transformation occurred or until the end of follow-up, at which point they were withdrawn from the study. The exposure factor was the level of EZH2 protein expression, and the outcome was the malignant transformation rate of OLK. Differences in EZH2 expression levels and transformation outcomes were analyzed. Results: There were no statistically significant differences between the high and low EZH2 expression groups in terms of age, sex, history of systemic disease, lifestyle habits, psychological status, diet, and sleep conditions (P > 0.05). Lesions in the high EZH2 expression group were mainly located on the ventral tongue, while in the low EZH2 expression group, they were more commonly found on the dorsal tongue and buccal mucosa. The malignant transformation rate was 28.6% (4/14) in the high expression group and 8.8% (8/91) in the low expression group; these differences were not statistically significant (P=0.053). In univariate Cox regression analysis, the risk of malignant transformation in the high EZH2 expression group was 3.647 times that of the low EZH2 expression group (HR = 3.647, 95% CI: 1.097-12.120, P<0.05). Kaplan-Meier survival analysis showed that over the 30-month follow-up period, the cancer-free survival rate in the high EZH2 expression group was 19.8% lower than in the low expression group, and the difference was statistically significant (P<0.05). In multivariate Cox regression analysis, only moderate and severe epithelial dysplasia were identified as independent risk factors for malignant transformation. The risk of malignant transformation in the moderate and severe dysplasia groups was 10.695 and 13.623 times higher, respectively, than in the mild dysplasia group (HR = 10.695, 95% CI: 2.270-50.396, P<0.05; HR=13.623, 95% CI: 1.918-96.774, P<0.05). EZH2 high expression was not an independent risk factor in the multivariate model (HR= 2.528, 95% CI: 0.752-8.500, P = 0.134). Conclusion High EZH2 protein expression is a risk factor for the malignant transformation of OLK but does not have independent predictive value.

Objective:To explore the preliminary results of using the UreteroPyeloVisClear Catheter (VCC) in the treatment of ureteral stones.Methods:A retrospective analysis was conducted on the clinical data of 18 patients with ureteral stones who underwent treatment with VCC at Beijing Tsinghua Changgung Hospital from November 2023 to March 2024. The cohort consisted of 15 men and 3 women, with a mean age of 53 years (range: 27-75 years). The preoperative CT measurements showed that the mean maximum stone diameter was 9 mm (range: 3-18 mm), and the mean maximum CT value of the stones was 870 HU (range: 260-1 480 HU). The distribution of stones was as follows: 3 cases in the upper ureter, 8 in the middle ureter, and 7 in the lower ureter. Gravity-assisted perfusion was used, and all patients underwent VCC combined with Holmium laser lithotripsy, with flexible ureteroscopy used if necessary. A ureteral stent was routinely placed for 2 weeks postoperatively. Perioperative conditions and complications were analyzed.Results:All 18 patients successfully underwent VCC lithotripsy, with one patient experiencing stone migration during the procedure. The average operation time was 53 minutes (range: 20-100 minutes), and the average lithotripsy time was 25.5 minutes (range: 6–60 minutes). There were no significant changes in serum creatinine or hemoglobin levels on the first postoperative day. The average hospital stay was 2 days (range: 1–3 days). One patient experienced a fever (maximum temperature of 38.5℃), which resolved with antibiotic treatment. The visual analogue scale (VAS) scores on postoperative day 1 were 0 for 15 patients, 2 for 1 patient, 3 for 1 patient, and 4 for 1 patient. No complications of Clavien-Dindo grade Ⅱ or higher were observed. At 1-month follow-up, the stone-free rate (SFR) was 100%(18/18), and no hydronephrosis was observed in the affected kidney.Conclusions:The results of this study indicates that VCC is a safe and effective method for treating ureteral stones, with a low incidence of postoperative complications and a high stone clearance rate.